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Regulation of SLCO4C1 transporter-mediated excretion of uremic toxins as a therapeutic strategy for Chronic Kidney Disease

Research Project

Project/Area Number 24890013
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

AKIYAMA Yasutoshi  東北大学, 東北メディカル・メガバンク機構, 非常勤講師 (70635557)

Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsトランスポーター / 尿毒症 / 尿毒素 / 慢性腎臓病 / SLCO4C1 / インドキシル硫酸 / 尿毒症物質
Research Abstract

Chronic kidney disease (CKD) is a global health problem that carries a substantial risk for cardiovascular morbidity and death. With the progression of CKD, various uremic toxins accumulate, subsequently causing renal damage and hypertension. Recently, we have revealed that kidney-specific organic anion transporter SLCO4C1 excretes uremic toxins, and the up-regulation of SLCO4C1 resulted in the reduction of blood pressure and renal inflammation in a CKD model. In this study, we revealed that indoxyl sulfate (IS), one of the best-known uremic toxins, inhibits the expression of SLCO4C1 through GATA3 and that removal of IS increases the SLCO4C1 expression. The combination therapy of, (1) activating the SLCO4C1 expression by statins, (2) reducing the plasma IS concentration by the administration of AST-120 and (3) administering GATA inhibitor, could be a more effective remedy for the excretion of uremic toxins and preservation of renal function in CKD patients.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (9 results)

All 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (3 results) Book (2 results)

  • [Journal Article] Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA32013

    • Author(s)
      Akiyama Y, Kikuchi K, Saigusa D, Suzuki T, Takeuchi Y, Mishima E, Yamamoto Y, Ishida A, Sugawara D, Jinno D, Shima H, Toyohara T, Suzuki C, Souma T, Moriguchi T, Tomioka Y, Ito S, Abe T.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 7 Pages: e66518-e66518

    • DOI

      10.1371/journal.pone.0066518

    • URL

      https://pure.teikyo.jp/en/publications/b41b65bc-bfe0-47fb-a7c3-8634d5a8a245

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 尿毒素の輸送とCKD2013

    • Author(s)
      2.秋山泰利、阿部高明
    • Journal Title

      腎と骨代謝

      Volume: 26 Pages: 223-229

    • Related Report
      2013 Final Research Report
  • [Journal Article] A metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS).2012

    • Author(s)
      Akiyama Y.
    • Journal Title

      Toxins

      Volume: 4 Issue: 11 Pages: 1309-1322

    • DOI

      10.3390/toxins4111309

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carrier-mediated transport of quercetin conjugates : Involvement of organic anion transporters and organic anion transporting polypeptides2012

    • Author(s)
      Wong C, Akiyama Y, Abe T et al.
    • Journal Title

      Biochem. Pharmacol

      Volume: 84 Issue: 4 Pages: 564-570

    • DOI

      10.1016/j.bcp.2012.05.011

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Indole-3-acetate Inhibits Erythropoietin Receptor Expression and Erythropoietin Signaling in vitro2013

    • Author(s)
      秋山 泰利
    • Organizer
      アメリカ腎臓学会
    • Place of Presentation
      アメリカ アトランタ
    • Related Report
      2013 Annual Research Report
  • [Presentation] A metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS)2012

    • Author(s)
      秋山泰利
    • Place of Presentation
      アメリカ腎臓学会
    • Related Report
      2013 Final Research Report
  • [Presentation] Metabolomic approach for clarifying the effect of AST-120 in 5/6 nephrectomized rats by capillary electrophoresis mass spectrometry2012

    • Author(s)
      秋山 泰利
    • Organizer
      アメリカ腎臓学会
    • Place of Presentation
      アメリカ サンディエゴ
    • Related Report
      2012 Annual Research Report
  • [Book] 慢性腎不全の病態トピックス9トランスポーター, 腎不全治療レシピ, 査読なし2013

    • Author(s)
      秋山泰利、阿部高明
    • Publisher
      医学出版
    • Related Report
      2013 Final Research Report
  • [Book] Annual Review腎臓2013

    • Author(s)
      秋山 泰利
    • Total Pages
      9
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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